Gene expression signature reflects differentiation differences rather than telomere maintenance mechanism

A gene expression signature purporting to distinguish between telomerase and ALT immortalization has recently been described (Lafferty-Whyte et al., 2009). This was obtained as the intersection of two independent signatures, one obtained from cell lines and the other from a panel of liposarcomas, which utilize different telomere maintenance mechanisms (TMMs). To assess the utility of this signature we used Affymetrix U133plus2.0 arrays to undertake a similar analysis of an independent collection of liposarcomas of defined TMM. In our dataset, the 297 gene signature causes the liposarcomas to cluster not on the basis of TMM, but rather on the basis of tumor histological subtype [Figure 1], consistent with the signatures reported by others (Matushansky et al., 2008). Expression analyses were performed on 38 liposarcoma tumors using Affymetrix U133plus2.0 arrays. Using cosine distance as a distance metric, hierarchical clustering of these samples was performed according to the expression levels of the 297 genes identified in the study by Lafferty-Whyte et al.